Background <p>Tuberculosis is a great public health concern. Disseminated tuberculosis carries a high mortality. Polyneuropathy is a rare but serious complication in patients with tuberculosis.</p> Case presentation <p>We report a 26-year-old female who presented with shortness of breath, anorexia, nausea, black stools, hoarseness, generalized weakness, and progressively worsening skin tingling sensation in the bilateral lower extremities. The patient rapidly developed respiratory failure, and required endotracheal intubation and mechanical ventilation. Severe disseminated tuberculosis was diagnosed, with <i>Mycobacterium tuberculosis</i> identified in the lung, gastrointestinal tract, and bone marrow (positive sputum smear for acid-fast bacilli, positive stool cartridge-based nucleic acid amplification test, and positive next-generation sequencing test in bone marrow biopsy). After two months of enhanced anti-tuberculosis treatment and intensive specialty nursing care, the patient continued to present with generalized weakness and tingling sensation in the bilateral lower extremities. The electromyography examination revealed multiple peripheral nerve damage, which is consistent with polyneuropathy. Finally, the patient recovered with persistent bilateral lower extremity weakness after the 13-month anti-tuberculosis treatment in addition to nutritional support, nursing care, and rehabilitation.</p> Conclusions <p>Polyneuropathy is rare, but can occur to patients with tuberculosis. Its clinical presentations can be easily masked when patients have multiple symptoms from serious illness, such as severe disseminated tuberculosis. Careful physical examination, necessary laboratory and imaging studies, appropriate treatments, and close follow-up re-evaluations should be applied to avoid long-term sequela of serious nerve damage and loss of function in these patients.</p>